Mitochondria are organelles important for both life and death. Mitochondria are major sources of cellular energy and are involved in processes resulting in apoptosis induction. The exact mechanism of apoptosis induction in mitochondria is not clarified in detail, but ‘mitocans’ are drugs known to induce cancer cell death by targeting mitochondria (Neuzil J et al., Molecular pharmacology (2007) 71: 1185-1199; Neuzil J et al., FEBS letters (2006) 580: 5125-5129). Mitocans destabilize mitochondria, thereby causing cytosolic release of apoptosis modulators (Green D R et al, (1998) Science 281:1309-1312). The indirect pro-oxidant activity of these agents in cancer cells is essential for their actions as anticancer agents (Dong L F et al., (2011) The Journal of biological chemistry 286: 3717-3728; Neuzil J et al., Molecular pharmacology (2007) 71: 1185-1199).
Meanwhile, mitochondria-targeted vitamin E (MVE) is the compound designed to accumulate within mitochondria. MVE is distributed within the heart, brain, liver, and muscle when administered; and affects mitochondrial dysfunction therein. MVE decreases mitochondrial oxidative damage, thereby inhibiting a range of human disorders, including neurodegenerative diseases, ischemia-reperfusion injury, and aging-associated dysfunctions. Mao et al reported that MVE decreases systemic oxidative stress parameters such as plasma SOD activity, attenuates hepatic oxidative stress and inhibits fat deposition (Mao G et al., (2011) The British journal of nutrition 106: 87-95; Mao G et al., The Journal of nutrition 140: 1425-1431). However, it has been reported that MVE increased ROS generation in cancer cells and acts as a prooxidant to suppress the proliferation of cancer cells (Dong L F et al., (2011) The Journal of biological chemistry 286: 3717-3728; Neuzil J et al., (2007) Molecular pharmacology 71: 1185-1199). For example, MVE modulates the expression of mitochondrial DNA transcripts and mitochondrial biogenesis. These changes subsequently result in arrest of cell proliferation (Truksa J et al., (2015) Antioxidants & redox signaling 22: 883-900). Therefore, MVE has controversial effects, i.e., antioxidant vs. prooxidant according to tissues and/or cells. For example, MVE exhibited protective effects in hepatic cells, but harmful effects in cancer cells. However, the functions of MVE in skin cells have not been identified.